Evidence of epigenetic alterations in children with FASD remains scarce. One study reported that children with PAE showed altered methylation status in genes related to protocadherins, glutamatergic synapses, and intercellular signaling, though these results were influenced by other factors, including sex and medications (Laufer et al., 2015). Interestingly, differential methylation was observed in imprinted regions, similar to changes seen to imprinted genes such as Igf2 and H19 (a long non-coding RNA) in mouse models of FASD (Laufer et al., 2013). Methylation changes to clustered protocadherin-related genes, important for cell adhesion and determination of neuronal identity, have been reported in mouse models of FASD as well (Chater-Diehl et al., 2016). Portales-Casamar et al. (2016) assessed genome-wide methylation patterns in Canadian children with FASD and found significant changes in 41 genes, with hypermethylation spanning genes associated with neurodevelopmental, mood, and substance abuse disorders. Clustered protocadherin genes were differentially methylated in this sample, similar to previous human and animal work (Chater-Diehl et al., 2016; Laufer et al., 2015). A factor limiting interpretation of these data is the relatively low increase in methylation (>5%)
